TheColoradoSpecializedCenterofResearchExcellenceonSexDifferences(CO-SCORE)isthematically focusedonBioenergeticandMetabolicConsequencesoftheLossofGonadalFunction.Theoverarching scientificobjectiveoftheCO-SCOREistoadvanceknowledgeoftheimpactofgonadalagingonthe regulationofbioenergetics,abdominaladiposity,andmetabolismbyconductingmechanistically-driven researchacrossthebasic-to-clinicaltranslationalspectrum.Thescientificpremiseisthatgonadalfailure mediatesbiologicalchangesthatincreaseriskforchronicdisease.Themostwell-studiedexampleofthisisthe accelerateddeclineinbonemineraldensityatmenopauseandtheassociatedosteoporosisrisk.However,the extenttowhichgonadalfailureincreasesriskforchronicdiseasesotherthanosteoporosisispoorly understood.Thisisaparticularlyimportantknowledgegapinwomen?shealth,becausegonadalfailureis inevitableinwomeninmid-life,butrareinmenuntilmuchlaterinlife.Theoverarchingeducationalobjective istoengagenewinvestigatorsinresearchalignedwiththethematicfocusoftheCO-SCORE.TheCO-SCORE willpromotementoredcareerdevelopmentandprovidetrainingonhowtoconductresearchthatappropriately addressessexasabiologicalvariable(SABV).Thesecentralobjectiveswillbeaccomplishedthroughthe followingAims:1)ThethreeCO-SCOREResearchProjects(basic,preclinical,andclinical)willadvance cutting-edge,paradigm-challengingtranslationalresearchonnovelmechanismspostulatedtocontributetothe increasedabdominaladiposityandassociatedmetabolicdysfunctionthatoccurintheestrogen-deficientstate;? 2)TheCareerEnhancementCore(CEC)willprovidearichtrainingenvironmenttoattractandsupport outstandingjuniorinvestigatorswithresearchinterestsrelatedtothethematicfocusoftheCO-SCORE. SCOREScholarsandPilotAwardeeswillbeselectedthroughacompetitiveprocessandparticipateina comprehensivecareerdevelopmentprogram;?3)TheLeadershipAdministrativeCore(LAC)willprovide infrastructuralsupportfortheResearchProjects,CO-SCOREPilotProjects,andtheCEC,including biostatistics,datamanagement,financialoversight,andadministrativesupport.Anevaluationspecialistwill useinnovativestrategiesforassessingwhethertheresearch,trainees,mentors,andtheCO-SCOREasa wholeareachievingahighlevelofimpactandreach;?and4)TheCO-SCOREwillpartnerwithotherCenters andProgramsatCU-AMCtoelevatethevisibilityandmulti-disciplinaryreachofwomen?shealthresearchand theimportanceofinvestigatingSABV.Activitieswilltargetbothscientificandlaycommunitiesatlocal,regional, andnationallevels.AchievingtheseAimswillpositiontheCO-SCOREasanationalleaderinourtargeted areasofwomen?shealthresearch,andtheCECasamodelprogramfortrainingjuniorinvestigatorsto appropriatelyintegrateSABVintotheirresearch,therebyaddressingtheultimategoaloftheSCOREprogram ofimprovingthehealthofwomen.